Simple within-stride changes in treadmill speed can drive selective changes in human gait symmetry.

Millions of people walk with asymmetric gait patterns, highlighting a need for customizable rehabilitation approaches that can flexibly target different aspects of gait asymmetry. Here, we studied how simple within-stride changes in treadmill speed could drive selective changes in gait symmetry. In Experiment 1, healthy adults (n = 10) walked on an instrumented treadmill with and without a closed-loop controller engaged. This controller changed the treadmill speed to 1.50 or 0.75 m/s depending on whether the right or left leg generated propulsive ground reaction forces, respectively. Participants walked asymmetrically when the controller was engaged: the leg that accelerated during propulsion (right) showed smaller leading limb angles, larger trailing limb angles, and smaller propulsive forces than the leg that decelerated (left). In Experiment 2, healthy adults (n = 10) walked on the treadmill with and without an open-loop controller engaged. This controller changed the treadmill speed to 1.50 or 0.75 m/s at a prescribed time interval while a metronome guided participants to step at different time points relative to the speed change. Different patterns of gait asymmetry emerged depending on the timing of the speed change: step times, leading limb angles, and peak propulsion were asymmetric when the speed changed early in stance while step lengths, step times, and propulsion impulses were asymmetric when the speed changed later in stance. In sum, we show that simple manipulations of treadmill speed can drive selective changes in gait symmetry. Future work will explore the potential for this technique to restore gait symmetry in clinical populations.

Dopamine facilitates the translation of physical exertion into assessments of effort.

Our assessments of effort are critically shaped by experiences of exertion. However, it is unclear how the nervous system transforms physical exertion into assessments of effort. Availability of the neuromodulator dopamine influences features of motor performance and effort-based decision-making. To test dopamine's role in the translation of effortful exertion into assessments of effort, we had participants with Parkinson's disease, in dopamine depleted (OFF dopaminergic medication) and elevated (ON dopaminergic medication) states, exert levels of physical exertion and retrospectively assess how much effort they exerted. In a dopamine-depleted state, participants exhibited increased exertion variability and over-reported their levels of exertion, compared to the dopamine-supplemented state. Increased exertion variability was associated with less accurate effort assessment and dopamine had a protective influence on this effect, reducing the extent to which exertion variability corrupted assessments of effort. Our findings provide an account of dopamine's role in the translation of features of motor performance into judgments of effort, and a potential therapeutic target for the increased sense of effort observed across a range of neurologic and psychiatric conditions.

The Cost of Gait Slowness: Can Persons with Parkinson's Disease Save Energy by Walking Faster?

BACKGROUND: Gait slowing is a common feature of Parkinson's disease (PD). Many therapies aim to improve gait speed in persons with PD, but goals are often imprecise. How fast should each patient walk? And how do persons with PD benefit from walking faster? There is an important need to understand how walking speed affects fundamental aspects of gait-including energy cost and stability-that could guide individualized therapy decisions in persons with PD. OBJECTIVE: We investigated how changes in walking speed affected energy cost and spatiotemporal gait parameters in persons with PD. We compared these effects between dopaminergic medication states and to those observed in age-matched control participants. METHODS: Twelve persons with PD and twelve control participants performed treadmill walking trials spanning at least five different speeds (seven speeds were desired, but not all participants could walk at the fastest speeds). Persons with PD participated in two walking sessions on separate days (once while optimally medicated, once after 12-hour withdrawal from dopaminergic medication). We measured kinematic and metabolic data across all trials. RESULTS: Persons with PD significantly reduced energy cost by walking faster than their preferred speeds. This held true across medication conditions and was not observed in control participants. The patient-specific walking speeds that reduced energy cost did not significantly affect gait variability metrics (used as proxies for gait stability). CONCLUSION: The gait slowing that occurs with PD results in energetically suboptimal walking. Rehabilitation strategies that target patient-specific increases in walking speed could result in a less effortful gait.

Persons post-stroke improve step length symmetry by walking asymmetrically.

BACKGROUND AND PURPOSE: Restoration of step length symmetry is a common rehabilitation goal after stroke. Persons post-stroke often retain the ability to walk with symmetric step lengths ("symmetric steps"); however, the resulting walking pattern remains effortful. Two key questions with direct implications for rehabilitation have emerged: 1) how do persons post-stroke generate symmetric steps, and 2) why do symmetric steps remain so effortful? Here, we aimed to understand how persons post-stroke generate symmetric steps and explored how the resulting gait pattern may relate to the metabolic cost of transport. METHODS: We recorded kinematic, kinetic, and metabolic data as nine persons post-stroke walked on an instrumented treadmill under two conditions: preferred walking and symmetric stepping (using visual feedback). RESULTS: Gait kinematics and kinetics remained markedly asymmetric even when persons post-stroke improved step length symmetry. Impaired paretic propulsion and aberrant movement of the center of mass were evident during both preferred walking and symmetric stepping. These deficits contributed to diminished positive work performed by the paretic limb on the center of mass in both conditions. Within each condition, decreased positive paretic work correlated with increased metabolic cost of transport and decreased walking speed across participants. CONCLUSIONS: It is critical to consider the mechanics used to restore symmetric steps when designing interventions to improve walking after stroke. Future research should consider the many dimensions of asymmetry in post-stroke gait, and additional within-participant manipulations of gait parameters are needed to improve our understanding of the elevated metabolic cost of walking after stroke.

Snail interacts with hPLSCR1 promoter and down regulates its expression in IMR-32.

Human phospholipid scramblase 1 (hPLSCR1) is a proapoptotic protein whose expression is deregulated in a variety of cancers cells. However till date the transcription regulation of hPLSCR1 is unknown. Transcriptional regulation of hPLSCR1 was studied by cloning the 5'-flanking region of hPLSCR1. Luciferase assays revealed that -1525 to -1244 region of hPLSCR1 was found to regulate its promoter activity. A putative Snail transcription factor (TF) binding site was found within the regulatory region of the promoter. Snail binding was found to down regulate the expression of hPLSCR1 both at the transcriptional and translational levels. Snail knock down using Snail-shRNA confirmed that down regulation of hPLSCR1 by Snail was specific. Point mutation studies confirm that the predicted Snail TF binds to -1123 to -1117 site. ChIP assay further confirms the physical interaction of Snail with hPLSCR1 promoter. This is the first report showing the transcriptional regulation of hPLSCR1 expression by Snail TF and its possible implications in cancer progression.